This fungal enzyme system comprises a multi-functional polyketide synthase (PKS) and an enoyl reductase. The PKS catalyses many of the chain building reactions of EC 2.3.1.85, fatty-acid synthase, as well as a reductive methylation and a Diels-Alder reaction, while the reductase is responsible for three enoyl reductions that are necessary for dihydromonacolin L acid production.

accessory protein LovC is needed: Loading of the megasynthase by malonyl-CoA is presumably followed by decarboxylation to yield the acetyl starter unit. Each round of Claisen condensation is catalyzed by the KS domain, whereas the growing polyketide is tethered to the phosphopantetheinyl arm of the ACP. After each condensation, the polyketide is subjected to a different combination of tailoring, which can include alpha-methylation by the MT domain, beta-ketoreduction by the KR domain, beta-dehydration by the DH domain, and alpha-beta-enoylreduction by the dissociated LovC. The different tailoring permutations after each round of chain extension yield a triene-containing hexaketide thioester that can undergo a stereospecific Diels-Alder cyclization to yield the decalin portion. After formation of the nonaketide, the chain is released to yield the ring-open form. In the absence of LovC, methylated hexa- and heptaketide pyrones are the primary products.

minimal polyketide synthase domains of subunit LovB as standalone proteins; the entire lovB gene is inserted into pET21a+ to create pSMa33, the LovB KS-MAT didomain, MAT, ACP, ACP-CON and CON are each amplified from pSMa33 and cloned into pET28a+